Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23290 | 70093;70094;70095 | chr2:178576264;178576263;178576262 | chr2:179440991;179440990;179440989 |
| N2AB | 21649 | 65170;65171;65172 | chr2:178576264;178576263;178576262 | chr2:179440991;179440990;179440989 |
| N2A | 20722 | 62389;62390;62391 | chr2:178576264;178576263;178576262 | chr2:179440991;179440990;179440989 |
| N2B | 14225 | 42898;42899;42900 | chr2:178576264;178576263;178576262 | chr2:179440991;179440990;179440989 |
| Novex-1 | 14350 | 43273;43274;43275 | chr2:178576264;178576263;178576262 | chr2:179440991;179440990;179440989 |
| Novex-2 | 14417 | 43474;43475;43476 | chr2:178576264;178576263;178576262 | chr2:179440991;179440990;179440989 |
| Novex-3 | None | None | chr2:None | chr2:None |
Information
Reported SAVs
| SNV | RS | DUET |
PolyPhen-2 |
Condel |
Rhapsody |
REVEL |
MVP |
Source |
MAF |
Disease |
Zygosity |
Site annotation |
mCSM PPI |
Predicted PPI site |
Comments |
AFR |
AMR |
AMS |
ASJ |
EAS |
EUR |
FIN |
MDE |
NFE |
SAS |
OTH |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/H | rs776114674  |
0.143 | 0.032 | N | 0.35 | 0.251 | 0.194818534648 | gnomAD-2.1.1 | 4.1E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.66E-05 | None | 0 | None | 0 | 0 | 0 |
| D/H | rs776114674 |
0.143 | 0.032 | N | 0.35 | 0.251 | 0.194818534648 | gnomAD-4.0.0 | 6.85754E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.52908E-05 | None | 0 | 0 | 0 | 0 | 0 |
| D/N | None | None | 0.822 | N | 0.475 | 0.182 | 0.218112801441 | gnomAD-4.0.0 | 6.85754E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.00476E-07 | 0 | 0 |
Saturation Mutagenesis
SAV |
AlphaMissense (IC) |
AlphaMissense Class (IC) |
AlphaMissense (N2AB) |
AlphaMissense Class (N2AB) |
mCSM |
mCSM class |
PolyPhen-2 |
PolyPhen-2 Class |
Rhapsody |
Rhapsody Class |
Condel |
Condel Score |
Site annotation |
mCSM PPI |
Predicted PPI site |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.5605 | ambiguous | 0.5661 | pathogenic | 0.008 | Stabilizing | 0.698 | D | 0.599 | neutral | N | 0.385762246 | None | None | N |
| D/C | 0.8713 | likely_pathogenic | 0.8594 | pathogenic | 0.01 | Stabilizing | 0.998 | D | 0.781 | deleterious | None | None | None | None | N |
| D/E | 0.6466 | likely_pathogenic | 0.6704 | pathogenic | -0.591 | Destabilizing | 0.656 | D | 0.497 | neutral | N | 0.455448831 | None | None | N |
| D/F | 0.9719 | likely_pathogenic | 0.9688 | pathogenic | 0.521 | Stabilizing | 0.978 | D | 0.797 | deleterious | None | None | None | None | N |
| D/G | 0.642 | likely_pathogenic | 0.6364 | pathogenic | -0.445 | Destabilizing | 0.822 | D | 0.531 | neutral | N | 0.45648898 | None | None | N |
| D/H | 0.8003 | likely_pathogenic | 0.816 | pathogenic | -0.017 | Destabilizing | 0.032 | N | 0.35 | neutral | N | 0.461510798 | None | None | N |
| D/I | 0.8455 | likely_pathogenic | 0.8284 | pathogenic | 1.234 | Stabilizing | 0.978 | D | 0.789 | deleterious | None | None | None | None | N |
| D/K | 0.9416 | likely_pathogenic | 0.9453 | pathogenic | -0.62 | Destabilizing | 0.86 | D | 0.587 | neutral | None | None | None | None | N |
| D/L | 0.922 | likely_pathogenic | 0.9111 | pathogenic | 1.234 | Stabilizing | 0.956 | D | 0.728 | prob.delet. | None | None | None | None | N |
| D/M | 0.965 | likely_pathogenic | 0.9605 | pathogenic | 1.708 | Stabilizing | 0.998 | D | 0.782 | deleterious | None | None | None | None | N |
| D/N | 0.4294 | ambiguous | 0.4582 | ambiguous | -1.075 | Destabilizing | 0.822 | D | 0.475 | neutral | N | 0.467263335 | None | None | N |
| D/P | 0.9835 | likely_pathogenic | 0.9814 | pathogenic | 0.853 | Stabilizing | 0.978 | D | 0.697 | prob.neutral | None | None | None | None | N |
| D/Q | 0.897 | likely_pathogenic | 0.9061 | pathogenic | -0.72 | Destabilizing | 0.956 | D | 0.576 | neutral | None | None | None | None | N |
| D/R | 0.9606 | likely_pathogenic | 0.9621 | pathogenic | -0.614 | Destabilizing | 0.956 | D | 0.749 | deleterious | None | None | None | None | N |
| D/S | 0.4866 | ambiguous | 0.5324 | ambiguous | -1.461 | Destabilizing | 0.193 | N | 0.349 | neutral | None | None | None | None | N |
| D/T | 0.7363 | likely_pathogenic | 0.7656 | pathogenic | -1.07 | Destabilizing | 0.754 | D | 0.575 | neutral | None | None | None | None | N |
| D/V | 0.5728 | likely_pathogenic | 0.5623 | ambiguous | 0.853 | Stabilizing | 0.97 | D | 0.752 | deleterious | N | 0.331293043 | None | None | N |
| D/W | 0.9951 | likely_pathogenic | 0.9946 | pathogenic | 0.424 | Stabilizing | 0.998 | D | 0.751 | deleterious | None | None | None | None | N |
| D/Y | 0.7597 | likely_pathogenic | 0.7502 | pathogenic | 0.686 | Stabilizing | 0.89 | D | 0.784 | deleterious | N | 0.467012618 | None | None | N |
Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.